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Article Open Access

Value of circulating free DNA methylation in the diagnosis of esophageal cancer: A systematic review and meta‑analysis

  • Authors:
    • Chenxiao Ma
    • Yixian Wang
    • Zuopan Ding
    • Xingxing Liang
    • Meng Yuan
    • Xuan Liu
    • Qiong Li
    • Hongbo Lv
    • Na Qiao
    • Xin Liu
  • View Affiliations / Copyright

    Affiliations: Department of Epidemiology and Statistics, School of Public Health, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Epidemiology and Statistics, School of Public Health, Jilin University, Changchun, Jilin 130021, P.R. China
    Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 478
    |
    Published online on: August 12, 2025
       https://doi.org/10.3892/ol.2025.15225
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Abstract

Liquid biopsy using circulating biomarkers has shown growing potential in cancer detection. The aim of the present study was to assess the application value of detecting the methylation level of circulating free (cf)DNA in the identification and diagnosis of esophageal cancer (EC), to lay a scientific foundation for its clinical application, and to provide statistically significant references for the detection process. A total of two researchers independently performed a comprehensive search of the PubMed, Web of Science, Cochrane Library, Embase and Scopus databases to identify all relevant studies on cfDNA in EC diagnosis as of July 25, 2024. A meta‑analysis was performed using MetaDiSc 1.4, Stata 16.0 and RevMan 5.4 software. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic rate (DOR) and area under the curve (AUC) values were determined. According to inclusion and exclusion criteria, a total of 14 studies with a total of 3,936 patients were included in the analysis. The pooled sensitivity and specificity, and PLR, NLR, DOR and AUC of cfDNA methylation in the diagnosis of EC were 0.83 [95% confidence interval (CI), 0.75‑0.89], 0.98 (95% CI, 0.95‑0.99), 34.57 (95% CI, 18.04‑63.44), 0.18 (95% CI, 0.12‑0.25), 197.25 (95% CI, 104.53‑372.20) and 0.98 (95% CI, 0.96‑0.99), respectively. In conclusion, cfDNA methylation demonstrates high diagnostic accuracy for early‑stage EC and may serve as a promising non‑invasive screening tool.
View Figures

Figure 1

Literature screening process. cfDNA,
circulating free DNA; EC, esophageal cancer.

Figure 2

Forest plots of pooled sensitivity
and specificity. CI, confidence interval.

Figure 3

SROC curve of circulating free DNA
for the diagnosis of esophageal cancer. The SROC curve is
symmetrical with no threshold effect. SROC, summary receiver
operating characteristic; AUC, area under the curve.
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Copy and paste a formatted citation
Spandidos Publications style
Ma C, Wang Y, Ding Z, Liang X, Yuan M, Liu X, Li Q, Lv H, Qiao N, Liu X, Liu X, et al: Value of circulating free DNA methylation in the diagnosis of esophageal cancer: A systematic review and meta‑analysis. Oncol Lett 30: 478, 2025.
APA
Ma, C., Wang, Y., Ding, Z., Liang, X., Yuan, M., Liu, X. ... Liu, X. (2025). Value of circulating free DNA methylation in the diagnosis of esophageal cancer: A systematic review and meta‑analysis. Oncology Letters, 30, 478. https://doi.org/10.3892/ol.2025.15225
MLA
Ma, C., Wang, Y., Ding, Z., Liang, X., Yuan, M., Liu, X., Li, Q., Lv, H., Qiao, N., Liu, X."Value of circulating free DNA methylation in the diagnosis of esophageal cancer: A systematic review and meta‑analysis". Oncology Letters 30.4 (2025): 478.
Chicago
Ma, C., Wang, Y., Ding, Z., Liang, X., Yuan, M., Liu, X., Li, Q., Lv, H., Qiao, N., Liu, X."Value of circulating free DNA methylation in the diagnosis of esophageal cancer: A systematic review and meta‑analysis". Oncology Letters 30, no. 4 (2025): 478. https://doi.org/10.3892/ol.2025.15225
Copy and paste a formatted citation
x
Spandidos Publications style
Ma C, Wang Y, Ding Z, Liang X, Yuan M, Liu X, Li Q, Lv H, Qiao N, Liu X, Liu X, et al: Value of circulating free DNA methylation in the diagnosis of esophageal cancer: A systematic review and meta‑analysis. Oncol Lett 30: 478, 2025.
APA
Ma, C., Wang, Y., Ding, Z., Liang, X., Yuan, M., Liu, X. ... Liu, X. (2025). Value of circulating free DNA methylation in the diagnosis of esophageal cancer: A systematic review and meta‑analysis. Oncology Letters, 30, 478. https://doi.org/10.3892/ol.2025.15225
MLA
Ma, C., Wang, Y., Ding, Z., Liang, X., Yuan, M., Liu, X., Li, Q., Lv, H., Qiao, N., Liu, X."Value of circulating free DNA methylation in the diagnosis of esophageal cancer: A systematic review and meta‑analysis". Oncology Letters 30.4 (2025): 478.
Chicago
Ma, C., Wang, Y., Ding, Z., Liang, X., Yuan, M., Liu, X., Li, Q., Lv, H., Qiao, N., Liu, X."Value of circulating free DNA methylation in the diagnosis of esophageal cancer: A systematic review and meta‑analysis". Oncology Letters 30, no. 4 (2025): 478. https://doi.org/10.3892/ol.2025.15225
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